NM_000020.3(ACVRL1):c.1336C>T (p.Gln446Ter) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Mar 21, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000479233.1

Allele description [Variation Report for NM_000020.3(ACVRL1):c.1336C>T (p.Gln446Ter)]

NM_000020.3(ACVRL1):c.1336C>T (p.Gln446Ter)

Gene:
ACVRL1:activin A receptor like type 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.13
Genomic location:
Preferred name:
NM_000020.3(ACVRL1):c.1336C>T (p.Gln446Ter)
HGVS:
  • NC_000012.12:g.51919074C>T
  • NG_009549.1:g.16657C>T
  • NM_000020.2:c.1336C>T
  • NM_000020.3:c.1336C>TMANE SELECT
  • NM_001077401.2:c.1336C>T
  • NP_000011.2:p.Gln446Ter
  • NP_000011.2:p.Gln446Ter
  • NP_001070869.1:p.Gln446Ter
  • LRG_543t1:c.1336C>T
  • LRG_543:g.16657C>T
  • LRG_543p1:p.Gln446Ter
  • NC_000012.11:g.52312858C>T
Protein change:
Q446*
Links:
dbSNP: rs1064794217
NCBI 1000 Genomes Browser:
rs1064794217
Molecular consequence:
  • NM_000020.2:c.1336C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_000020.3:c.1336C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077401.2:c.1336C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000568238GeneDxcriteria provided, single submitter
Likely pathogenic
(Mar 21, 2017)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000568238.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The Q446X variant in the ACVRL1 gene has been reported in one individual with HHT (McDonald et al., 2011). The Q446X variant is predicted to cause loss of normal protein function by protein truncation, as the last 58 amino acid residues of the protein are lost. Other nonsense variants in the ACVRL1 gene, including several downstream, have been reported in Human Gene Mutation Database in association with HHT (Stenson et al., 2014). Furthermore, the Q446X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Nevertheless, this variant lacks a sufficient number of probands, segregation data, and functional studies to be able to definitively determine is pathogenicity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 25, 2021

Support Center